The overarching objective of this Project is to identify genetic variants that are associated, both as main effects and via interactions with exposure to environmental stressors, with incident cardiovascular events or coronary artery disease (CAD). To accomplish this goal, we will evaluate genes found associated in Projects 1 and 2 with CVD endophenotypes or in Project 3 with hypertension or type II diabetes (T2D), for associations with incident cardiovascular events and angiographically documented CAD in the CATHGEN sample of approximately 10,000 patients who have undergone cardiac catheterization at Duke since 2001. CATHGEN is a unique resource of biological samples collected at time of cardiac catheterization combined with a carefully adjudicated clinical database comprising angiographically-defined extent and anatomical distribution of coronary artery disease, extensive clinical data on CHD risk factors, and annual follow-up for evaluation of incident cardiovascular events. The CATHGEN investigators, under non-overlapping support from their NHLBI grant, will be evaluating a broad range of genes that are biologically plausible contributors to CHD pathogenesis and/or course or have been reported to be associated with CHD for associations with CAD and clinical events. Therefore, another aim of this Project, will be to collaborate with Projects 1, 2 and 3 to determine whether any genetic variants we fmd associated with CAD or clinical events in the CATHGEN sample are also associated with CVD endophenotypes, hypertension and/or T2D in their samples. As with Project 3, this Project provides the opportunity to take the critical step of translating gene associations with CVD endophenotypes into documented impact on disease endpoints.

Public Health Relevance

The knowledge gained can be used to identify persons at risk who can be selected for behavioral and/or pharmacologic interventions that target the CVD endophenotypes via which gene effects on pathogenesis or disease course are mediated, with the goals or preventing disease and improving prognosis once disease is present

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL036587-22
Application #
8378680
Study Section
Special Emphasis Panel (ZHL1-PPG-Z)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
22
Fiscal Year
2012
Total Cost
$415,668
Indirect Cost
$150,911
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette et al. (2016) Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One 11:e0152670
McGarrah, Robert W; Craig, Damian M; Haynes, Carol et al. (2016) High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. Atherosclerosis 246:229-35
Haberstick, Brett C; Boardman, Jason D; Wagner, Brandon et al. (2016) Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health). PLoS One 11:e0148373
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2016) Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults. Clin Psychol Sci 4:272-286
Haberstick, Brett C; Smolen, Andrew; Williams, Redford B et al. (2015) Population frequencies of the Triallelic 5HTTLPR in six Ethnicially diverse samples from North America, Southeast Asia, and Africa. Behav Genet 45:255-61
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2015) The relation between insecure attachment and posttraumatic stress: Early life versus adulthood traumas. Psychol Trauma 7:324-32
Ward-Caviness, Cavin K; Kraus, William E; Blach, Colette et al. (2015) Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients. Environ Health Perspect 123:1007-14
Singh, Abanish; Babyak, Michael A; Brummett, Beverly H et al. (2015) Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene. Genet Epidemiol 39:489-97
Boyle, Stephen H; Georgiades, Anastasia; Brummett, Beverly H et al. (2015) Associations between central nervous system serotonin, fasting glucose, and hostility in African American females. Ann Behav Med 49:49-57
Davey, Adam; Siegler, Ilene C; Martin, Peter et al. (2015) Personality Structure Among Centenarians: The Georgia Centenarian Study. Exp Aging Res 41:361-85

Showing the most recent 10 out of 200 publications